Humanized anti-CD123 antibody facilitates NK cell antibody-dependent cell-mediated cytotoxicity (ADCC) of Hodgkin lymphoma targets via ARF6/PLD-1.
ADP-Ribosylation Factor 6
ADP-Ribosylation Factors
/ antagonists & inhibitors
Animals
Antibodies, Monoclonal, Humanized
/ pharmacology
Antibody-Dependent Cell Cytotoxicity
/ drug effects
Antineoplastic Agents, Immunological
/ pharmacology
Biomarkers
Cell Degranulation
Cell Line
Cytokines
/ metabolism
Exocytosis
Humans
Interleukin-3 Receptor alpha Subunit
/ antagonists & inhibitors
Killer Cells, Natural
/ drug effects
Mice
Proto-Oncogene Proteins c-jun
/ genetics
Journal
Blood cancer journal
ISSN: 2044-5385
Titre abrégé: Blood Cancer J
Pays: United States
ID NLM: 101568469
Informations de publication
Date de publication:
15 01 2019
15 01 2019
Historique:
received:
15
07
2018
accepted:
13
12
2018
revised:
31
10
2018
entrez:
17
1
2019
pubmed:
17
1
2019
medline:
31
12
2019
Statut:
epublish
Résumé
CD123 (IL-3Rα) is frequently expressed by malignant Hodgkin lymphoma (HL) cells. Naked monoclonal antibodies (mAb) against HL lack clinical benefit, partially due to absence of natural killer (NK) cells in the tumor microenvironment. Here we show that the combination of a fully humanized anti-CD123 mAb (CSL362) and high-affinity Fcγ-receptor NK-92 cells (haNK) effectively target and kill HL cells in vitro. First, we confirmed high expression of CD123 in 2 of the 3 HL cell lines (KM-H2 and L-428), and its absence in NK cells. Cytotoxicity of haNK cells against CD123-positive HL cells was significantly higher in the presence of CSL362. This was also shown with IL-15-activated primary NK cells, although haNK cells showed a 10.87-fold lower estimated half-maximal stimulatory effective concentration (EC
Identifiants
pubmed: 30647406
doi: 10.1038/s41408-018-0168-2
pii: 10.1038/s41408-018-0168-2
pmc: PMC6333842
doi:
Substances chimiques
ADP-Ribosylation Factor 6
0
Antibodies, Monoclonal, Humanized
0
Antineoplastic Agents, Immunological
0
Biomarkers
0
Cytokines
0
Interleukin-3 Receptor alpha Subunit
0
Proto-Oncogene Proteins c-jun
0
ADP-Ribosylation Factors
EC 3.6.5.2
ARF6 protein, human
EC 3.6.5.2
Arf6 protein, mouse
EC 3.6.5.2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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